Autism and Genetics: A Q&A About What We Know

There’s good news coming from autism researchers at a rapid pace.

Almost monthly, we hear about new genes tied to autism spectrum disorders. Still, our understanding of the genetics of autism is years behind our understanding of how genetics affects cancer, for example. Charis Eng, MD, PhD, Chair of Cleveland Clinic's Genomic Medicine Institute and Thomas Frazier, II, PhD, Director of the Children's Hospital Center for Autism, are working to investigate autism and genetic related factors. Dr. Eng has discovered a gene that predisposes people to certain kinds of cancer that can also be linked with autism.

With that in mind, they sat down to answer some questions about what we know now — and what we will know in the future.

When it comes to autism and genetics, how much do we know?

Dr. Frazier: We’ve known for a while — about 30 years — that autism is a highly genetic disorder. But we never really had a good sense for what was happening. Was it one gene, or were there many genes? Well, the latest estimate is that there are probably at least 500 genes and maybe 1,000 that are involved in autism.

Dr. Eng: To put that into perspective, up to 100 of those genes have been discovered, so we have about 900 more to go!

How often is genetics involved in autism?

Dr. Frazier: There are estimates that at least 90 percent of individuals on the autism spectrum have a strong genetic component — but even then, a child’s environment might play a part, too.

Dr. Eng: On top of that, we want to know more about the way genes interact. The PTEN gene, which I study, and the genes responsible for syndromes like Fragile X and tuberous sclerosis complex are “strong” genes. They may act on their own. But many of those hundreds of other genes are “weaker.” They probably need to act together. Knowing how genes interact will make it easier to diagnose and treat different types of autism.

Dr. Frazier: We also want to know more about how proteins interact. It’s like the “telephone game” kids play. One protein has an effect on the next protein, then that next protein adds in its own effect, and so on. All the proteins along the way shape the final message.

So what does this mean for concerned parents? Are there tests available now for specific genes?

Dr. Frazier: There are. You know, in an ideal world, we’d have all of our children with autism see medical geneticists. But we’re not quite there yet. In practice, we try to identify patients with the highest risk for having a genetic cause and have them see a genetic counselor or a medical geneticist.

Dr. Eng: I would add that the “red flags” for autism risk are not quite the same as the red flags we look for with genetic risk of cancer, for example.

Dr. Frazier: That’s right. For example, about 20 percent of kids with autism have a large head circumference. That’s a red flag because it shows an increased risk for a PTEN mutation. It also may be a sign of another brain problem like hydrocephalus that requires further evaluation and possibly treatment.

How does that information change things for parents and kids?

Dr. Eng: It really depends on the gene. If it is PTEN, for example, that may change how a doctor intervenes for autism. And of course we will want to screen carefully for cancer because there’s a higher risk with PTEN than with some of the other genes.

Dr. Frazier: Other examples include genetic syndromes like Prader-Willi and Angelman syndromes, which have been strongly associated with autism, too. Once you identify the gene or syndrome, you can not only monitor medical risks but also develop a better understanding of their treatment needs.

For example, people with one type of Prader-Willi syndrome may be more socially motivated. They might show greater benefit from natural social reinforcement as they acquire skills. On the other hand, some genetic syndromes are associated with “gaze aversion,” where people look away when speaking to others. In these cases, we may not want to force eye contact in situations that would only raise anxiety and frustration.

Dr. Eng: It goes back to what we always say about genetic counseling: We want to empower patients and their families. Even if we have a lot to learn, what we know can really help us treat and manage your disease.